This is a competitive supplemental grant proposal to continue the clinical-laboratory studies using specimens from a national clinical trial chaired by the principal investigator entitled: "Phase Ill Randomized Study of Chimeric antiGD2 in High Risk Neuroblastoma Following Myeloablative Therapy and Autologous Stem Cell Rescue." Newly diagnosed patients with-high risk neuroblastoma will receive uniform induction chemotherapy, surgery, followed by autologous stem cell transplantation (ASCT). They will then be randomized to 13-cis- retinoic acid +/- immunotherapy. The latter consists of a human-mouse chimeric anti-GD2, chl4.18, and cytokines (GM-CSF alternating with IL-2). This competitive supplemental grant is prompted by an increase in the sample size for the Phase 3 study in response to a request from FDA that the Clinical Oncology Group (COG) consider possible future licensure of chl4.18 should its efficacy be proven by the Phase 3 study. Accordingly, this protocol was amended to increase the sample size from 359 to 423, and accrual time from 3.8 to 5 years with a total of 8 years including 3 year follow-up. In general, the anti-tumor activities of anti-GD2 antibodies rely on complement dependent cytotoxicity and antibody dependent cellular cytotoxicity (ADCC). Following ASCT, however, there is a paucity of data regarding the ADCC capabilities of neutrophils and lymphocytes. In addition to ADCC, CD56+ lymphocytes which consist of NK (CD3-) and NK-T (CD3+) cells are believed to be major players in immune surveillance and antitumor activities in response to cytokines. Although NK was said to recover rapidly after transplant, little is known about NK-T cells and the expression of NK activation and inhibitory receptors post-ASCT. Another intriguing issue is the role of FcR genotyping in ADCC activities and clinical outcome. Thus, along with the Phase 3 clinical trials, blood samples will be obtained at specified time points and shipped to the principal investigator's lab for the following specific studies: (1) serial monitoring of ADCC activities mediated by neutrophils and mononuclear cells to determine whether they are operational in the post-transplant setting and whether IL-2 exposure affects neutrophil mediated ADCC;(2) serial monitoring of number of NK cells, NK-T cells, NK activity, and expression of NK activation and inhibitory receptors;(3) exploring the relationship between immune effector cell number, functions and expression of NK receptor molecules with EFS in patients;and (4) examining the correlation of the genotypes of FcgRlllA and FcgRllA with ADCC activity and clinical outcome in patients randomized to immunotherapy. These studies should yield important information crucial to the design of future passive immunotherapy of cancer in the setting of minimal residual disease following single or double (tandem stem transplantation) myeloablative therapy.